England secured a 13-6 win at Murrayfield but Botha knows that will count for little if they slip up in the Stadio Olimpico.
Botha said: "It will be a big battle. Italy are one of the sides which has made massive strides over the past few years. They are not a wooden-spoon team any more.
"At home in their new stadium they will be up for the challenge with 70,000 fans behind them."
Botha believes England can go on to build "something special" after laying the foundation stones with last weekend's breakthrough victory over Scotland.
Botha revealed how England's first Murrayfield triumph in eight years was inspired by the unlikely figure of pop star Lana del Rey.
The American singer's top-10 hit Video Games was playing as the England squad walked into the Murrayfield changing room - and everyone in the squad new what that meant.
Stuart Lancaster had used the song to soundtrack a motivational highlights video - one of the tools England's interim coach used to unite his new-look squad.
England battled to a 13-6 victory in Edinburgh and are now anxious to build on that gutsy performance against Italy in Rome this weekend.
"The bond we have created is something that we showed on Saturday and it is building towards something special," said Botha, who will be named in the England team when it is announced today.
"Stuart got it spot on with the build up of emotions. This song was playing in the dressing room as you walked in.
"It was the backing track to a highlights package that had been made for us featuring all the players.
"It made the hairs stand up. It gave you the feeling you are ready for this.
"It was a brilliant occasion on Saturday at Murrayfield and to be facing something like that again will be a brilliant challenge."
The games and the stadia keep getting bigger for Botha, who moved from South Africa to England in October 2004 after National League Three club Bedford Athletic were the only one of 20 clubs to answer his letter.
Botha moved on to the Bedford Blues in 2006 and then, in 2010, saw a message on Facebook that Saracens were looking to bolster their second-row options.
The interview panel was daunting - director of rugby Brendan Venter and Morne du Plessis, the former South Africa international and manager of the 1995 World Cup-winning Springboks.
Botha's hunger impressed Du Plessis, who immediately recommended Saracens sign the former carpet washer and asbestos stripper despite having never seen him play.
When Saracens chief executive Edward Griffiths rang to offer Botha the deal, he had not even left the car park.
"Brendan Venter was at the meeting with Morne du Plessis," Botha said.
"I said 'today is the biggest day of my life and career and to be sitting here so close to actually achieving (a move to the Premiership) is a massive opportunity and one I really want'.
"I later found out that when I left the room Brendan Venter turned to Morne du Plessis and asked him what he thought.
"He said he didn't know much of my rugby and hadn't seen any videos but he would sign me because I wanted it so much. That is what swayed them, the fact that I had such a hunger to be successful at that level."
The desire sensed by Du Plessis comes from Botha's setbacks.
At just under 17 stone he was deemed too small for the second row by the Stormers - but he is now over 18 stone and was a key figure in England's defensive effort at Murrayfield.
"I always believed I could play Test rugby, I always had a deep down belief," said Botha.
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